Arq Neuropsiquiatr 2006;64(4):1041-1042
D e p a rtments of Neuro l o g y1, Internal Medicine2, Gastro e n t e ro l o g y3, Hematology4of the Escola Paulista de Medicina - Universidade
Federal de São Paulo, São Paulo SP, Brazil (UNIFESP).
Received 3 May 2006, received in final form 2 August 2006. Accepted 18 September 2006.
Dr. André Carvalho Felício - Avenida Bosque da Saúde 834 / 193 - 04142-081 São Paulo SP - Brasil. E-mail: cf.andre@terra.com.br
CEREBRAL VENOUS THROMBOSIS AND HEPATITIS
Case report
André Carvalho Felício
1, Márcia Maiumi Fukujima
2, Jose Antônio Fiorot Jr
1,
Gilmar Fernandes do Prado
1, Roberto José de Carvalho Filho
3,
Celso Arrais Rodrigues
4, Vânia Maris Morelli
4, Dayse Maria Lourenço
4ABSTRACT - Among the many infective causes of cerebral venous thrombosis (CVT), viral hepatitis is been re g a rded as a rare associated condition. We re p o rt on a 56-years-old man presenting CVT associated with hepatitis B and C coinfections outlining probable pathogenic mechanisms. We suggest that virus B and C serology should be performed in the cases of cerebral venous thrombosis with unknown etiology.
KEY WORDS: cerebral venous thrombosis, hepatitis B virus, hepatitis C virus.
Trombose venosa cerebral e hepatite: relato de caso
RESUMO - Dentre as várias causas infecciosas de trombose venosa cerebral (TVC), a hepatite viral tem sido reconhecida como causa rara de TVC. Relatamos sobre um homem de 56 anos com TVC associada a coin-fecção pelos vírus B e C da hepatite, ressaltando possíveis mecanismos patogênicos. Sugerimos que soro l o-gia para vírus da hepatite B e C deveria ser solicitado em todos os casos de TVC de origem indeterm i n a d a .
PALAVRAS-CHAVE: trombose venosa cerebral, vírus da hepatite B, vírus da hepatite C.
The main recognized causes or predisposing con-ditions to cerebral venous thrombosis (CVT) can be divided into two groups: infectious (either local or systemic) and non-infectious causes1 - 3. There is also
a third group without specific etiology, which may c o rrespond to 20% to 35% of the total causes4.
C h ronic hepatitis C virus (HCV) infection has been c o n s i d e red as a rare cause of cerebral venous thro m-bosis5-10.
We re p o rt a case of such association and discuss possible physiopathogenic mechanisms.
CASE
A 56-year-old white man was admitted to our hospital with a 15-day history of headache worsening with consid-erable change in its frequency and intensity patterns. He was a chronic daily headache suff e rer taking amitry p t i l i n e 75 mg and propranolol 80 mg per day and had already tak-en several abortive treatmtak-ent regimtak-ens. Four days before admission he had two episodes of focal motor seizure. His past history included heavy smoking and drinking. He took intravenous cocaine for 20 years until 12 years ago. He also had occasional bisexual relations. General physical examnation was unremarkable. Neurological exam abnorm a l i-ties included left mild hemiparesis. Pain relief medication was initiated as well as carbamazepine 600 mg per day.
Routine blood and urine exams were unremarkable. On c e rebral spinal fluid (CSF) the initial pre s s u re was 33 cm/H2O
with cell count and biochemistry within normal parameters. Chest radiograph was normal such as cranial comput-ed tomography scan (CT). Cranial magnetic resonance imag-ing (MRI) indicated superior sagittal and left transverse sinuses thrombosis associated to corpus callosum and right parietal hemorrhagic venous infarcts. New blood sample was taken in order to investigate pos sible secondary e ti-ologies and on that time venous non-fractionated heparin was initiated.
Anticoagulation was maintained with warfarin for six months and then suspended. Hepatological follow-up was initiated but the patient refused liver biopsy. He is still re f e r-ring headache but less frequently and less intense and takes phenobarbital 100 mg per day. General and neuro l o g i c a l exams are unremarkable.
The patient signed informed consent allowing his per-sonal data publication.
DISCUSSION
T h e re is considerable evidence that pro t h ro m b o t-ic states may develop soon after atero t h rombott-ic or c a rdioembolic cerebral infarct. Cerebral venous thro m-bosis, on the other hand, is usually a consequence of these procoagulant conditions11-13.
Tough re p o rted mechanisms of cerebral venous t h rombosis in patients with hepatitis B and C are not fully understood, there is growing evidence that these v i ruses alone or in combination with a series of oth-er factors may shift the delicate pro c o a g u l a n t / t h ro m-bolysis balance toward thrombosis10.
It is known that hepatitis C virus (HCV) infection may be associated with anticardiolipin antibodies. Thus, HCV might lead to thrombotic complications and should be considered as one of the antiphospho-lipid syndrome possible causes6 , 7. In the present case,
a n t i c a rdiolipin antibodies were negative as well as other autoantibodies.
Subjects with chronic hepatitis C who are receiv-ing interf e ron-alpha (INF-alpha) have an incre a s e d risk of diabetes mellitus and hypert r i g l i c e r i d e m i a1 4 , 1 5.
T h e re f o re, INF-alpha can be considered as a risk fac-tor for hypercoagulable states. In addition, either INF-alpha or HCV have been re p o rted to induce a variety of antibodies, not only anticardiolipin but also cryoglobulins, rheumatoid factor, antinuclear, antismooth muscle, anti-LKM and antithyre o g l o b u-l i n5 , 1 6. Since the diagnosis of hepatitis came while
in-vestigation was carried out our patient was not re-ceiving INF-alpha or any other medication that could increase thrombosis risk.
In spite of the possible relationship between HCV and antiphospholipid syndrome, other data suggest that HCV,per se,might be responsible for thro m b o t-ic events8. It is speculated that the HCV envelope
pro-tein has a procoagulant activity and that the viru s genome encodes serine proteases that could also act as procoagulant17.
In this case, the possibility of a pathogenic role of occult hepatitis B virus (HBV) infection can not be ful-ly discarded, since molecular tests for HBV DNA detec-tion have not been done1 8. Nonetheless, we could
find only one re p o rt of cerebral venous thro m b o s i s
associated to hepatitis B (HBV). That was the case of a 43-year-old male who presented with seizures and had a previous history of HBV. He developed a left transversal sinus thrombosis associated to left tem-poral posterior hemorrhagic infarct. On investiga-tion, anticardiolipin antibodies were negative tough t h e rewas an antithrombin III and protein C deficien-c y9. In the present case, there was also the
associa-tion between sinus thrombosis and hemorrh a g i c venous infarct. However, antithrombin and pro t e i n C levels were normal.
To conclude, since our patient was not taking INF-alpha and any identifiable procoagulant cause was recognized, the hypothesis of HCV (and maybe HBV) as thrombogenic agent deserves further attention. We also suggest that HCV and HBV tests should be routinely included in the investigation of cere b r a l venous thrombosis of unknown etiology.
REFERENCES
1. Silva GS, Almeida MO, Félix EPV, Fukujima MM, Ferraz HB, Gabbai AA. Trombose venosa cerebral e homocistinúria. Arq Neuropsiquiatr 2001;59:815-816.
2. Canhão P, Ferro JM, Lindgren AG, Bousser M-G, Stam J, Barinagarre-menteria F and for the ISCVT Investigators. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005;36:1720-1725. 3. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med
2005;352:1791-1798.
4. Marques MCP, Pires LA, Damasceno CA, Felício AC, Atala A, Franco GM. Trombose da veia de Galeno: relato de caso. Arq Neuropsiquiatr 2003;61:285-287.
5. Pawlotsky JM, Yahia MB, A n d re C, et al. Immunological disorders in C virus chronic active hepatitis: a prospective case-control study. Hepatology 1994;19:841-848.
6. Prieto J, Yuste JR, Beloqui O, et al. A n t i c a rdiolipin antibodies in chro n-ic hepatitis C: impln-ication of hepatitis C vírus as the cause of the antiphospholipid syndrome. Hepatology 1996;23:199-204.
7. Kesler A, Pomeranz IS, Huberman M, Novis B, Kott E. Cerebral venous t h rombosis and chronic active hepatitis as a part of the antiphospho-lipid syndrome. Post Med J 1996;72:690-692.
8. Violi F, Ferro D, Basili. Hepatitis C virus, antiphospholipid antibodies, and thrombosis. Hepatology 1997;27:782.
9. Pérez S, Casado I, García I, Gómez M, Ramirez JM, Luengo E. Infarto hemorrágico por trombosis del seno transverso como complicación de la cirrosis. Rev Neurol 1999;29:1355.
10. Nadir A, Amin A, Chalisa N, van Thiel DH. Retinal vein thro m b o s i s associated with chronic hepatitis C: a case series and review of the lit-erature. J Viral Hepat 2000;7:466-470.
11. Beltrán-Blasco I. Trombosis venosas intracraneales. Rev Neurol 1997; 25:569-575.
12. B a r i n a g a r rementeria F, González-Duarte A, Cantú-Brito C. Estados protrombóticos e isquemia cerebral. Rev Neurol 1998;26:85-91. 13. van Gijn J. Cerebral venous trombosis: patogenesis, presentation and
prognosis. J R Soc Med 2000;93:230-233.
14. B a ron S, Tyring SK, Fleishmann WR, et al. The interferons: mechanisms of action and clinical oimplications. JAMA 1991;266:1375-1383. 15. Fabris P, Betterle C, Greggio NA. Insulin-dependent diabetes mellitus
during- i n t e r f e ron therapy for chronic viral hepatitis. Hepatol 1998;28: 514-517.
16. Saracco G, Touscoz A, Durazzo M. Auto antibodies and response to -i n t e r f e ron -in pat-ients w-ith chron-ic v-iral hepat-it-is. Hepatology 1990;11 : 339-343
17. Bezan JF, Fletterick RJ. Detection of a trypsin like serine protease domain in flaviviruses and pestiviruses. Virology 1989;171:637-639. 18. B rechot C, Thiers V, Kremsdorf D, Nalpas B, Pol S, Paterlini-Brechot P.
Persistent hepatitis B virus infection in subjects without hepatitis B sur-face antigen: clinically significant or purely "occult"? Hepatology 2001; 34:194-203.
